1. Field of the Invention
The present invention generally pertains to software and systems for managing clinical trials, and, in more particular, concerns a method and system for providing real-time clinical trial enrollment data via a distributed software architecture.
2. Background Information
Clinical trials are a critical aspect in the development of any new drug, and are also used to verify the safety and efficacy of treatment modalities, such as new surgical techniques. For example, in order to obtain FDA (Federal Food and Drug Administration) approval, the safety, efficacy and other effects of an investigational drug are evaluated through observation and survey of various test subjects who are provided with the drug (or concurrent controls, such as a placebo) during clinical trials of the drug. Typically, clinical trials take several years and cost millions of dollars.
Clinical trials typically involve three phases, named Phase I, Phase II, and Phase III. The process starts when a sponsor files an application, called Investigational New Drug Application (IND), to conduct a Phase I clinical trial on human subjects. Absence of objection, the Phase I clinical trial(s) are performed. Phase I trials typically involve a small group of test subjects (e.g., less than 50), and are primarily designed to characterize the performance of the drug, with emphasis on safety. Generally, the subjects participating in a Phase I clinical trial are healthy volunteers , A Phase I trial is designed to determine what happens to the drug in the human body—how it is absorbed, metabolized, and excreted. A Phase I study will investigate side effects that occur as dosage levels are increased. Administration of Phase I studies are typically performed at a very small number of sites, such as a few (or even one) research hospitals.
If the drug is shown to be safe (based on Phase I human trials and toxicology tests on animals), the sponsor will move on toPhase II clinical trials using a larger subject group. Phase II is designed to show the efficacy of the drug, and is typically performed with several hundreds of subjects, using a small to moderate number of sites. Phase II trails are usually controlled studies, using one or more concurrent controls, such as dosage comparison, placebo, no-treatment, active treatment, and historical control.
If the results of Phase II show promise, the sponsor will move on to Phase III trials. Phase III clinical trials are designed to project the behavior of the drug on large targeted populations, including efficacy, safety, and side effects. One reason for Phase III trials is to statistically remove (ideally) any anomalies that may result from a Phase II study group that doesn't adequately represent a cross-section of the population targeted for the drug. Accordingly, Phase III studies are carried on larger subject populations (typically 500-2000+), preferably using a significant number of geographically-disperse and/or ethnically-diverse sites so that the results of the clinical trial better reflect the actual effects on the targeted population in response to taking the drug.
Each clinical trial is managed by a sponsor, comprising an individual, company, institution, or organization that also takes responsibility for the initiation and/or financing of the clinical trial. Typically, the sponsor will be a pharmaceutical or biotech company, or other entity that has developed the drug, or has a substantial interest in the drug or an existing drug proposed for a new use. Sponsors are also responsible for applying to regulatory agencies for permission to conduct clinical trails on human subjects, filing the results of the trials, and applying for FDA approval at the end of the clinical trials. These tasks are typically performed by a team, including a clinical director, clinical manager, and one or more clinical research associates (CRAs).
Each clinical trial is conducted in accordance with a protocol. A protocol is a document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial. The protocol states what will be done in the study and why. It outlines how many subjects will take part in the study, what types of subjects may take part, what tests they will receive and how often, and the treatment plan. The trial protocols are typically written by clinical trial administrators and other personnel working for the sponsor based on standardized and mandated methodologies and input from physicians who specialize in medical areas pertaining to the drug's intended use. Oftentimes, the protocol for a given phase will change over the course of the trial, based on information derived from earlier testing, leading to Protocol Amendments or Protocol Addendi.
The actual tests identified by the protocol are administered and monitored by qualified medical professionals (known as investigators), who are often physicians, and their staffs (e.g., nurse practitioners). An investigator is the person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a given site, the investigator who is the responsible leader of the team is called the principal investigator. A site is a team of individuals, headed by a principal investigator, who conduct clinical trials based on a protocol in specified locations, called sites.
Typically, each CRA is assigned to manage one or more investigators at one or more sites to ensure clinical trial is conducted in accordance with regulatory guidance and Good Clinical Practice (GCP). Examples of the tasks normally perform by CRA are: collecting regulatory documents, conducting site visits to retrieve Case Report Form, and writing trip reports.